The project proposed in this application has as its goal the determination of the relation between temperature and the apparent diffusion coefficient (ADC) of living tissue measured with diffusion- weighted echo-planar magnetic resonance (MR) imaging during hyperthermia treatment. This information on the temperature dependence of the tissue ADC has the potential to improve the delivery of hyperthermia therapy by providing: (a) measures of changes in the distribution of the temperature in malignant and normal tissues and (b) the potential to monitor possible tissue changes occurring during the therapy due to thermal damage. The project will have three phases: In Phase 1 we will optimize the heating devices (rf and ultrasonic), imaging coils, pulse sequences and computer programs for the performance of echo-planar diffusion-weighted MRI on a whole body MRI system for use on animal and human subjects. Also during Phase 1 we will begin studies with diffusion-weighted EPI on anesthetized animals (dogs) using equipment development to allow simultaneous MRI and hyperthermia. This work will thus lead into Phase 2 during which we will measure the relationship in anesthetized animals between temperature (measured invasively with fiberoptic probes) and the change in the ADC for normal tissues and spontaneously occurring canine tumors. Our hypothesis is that changes in temperature will result in reproducible, nearly linear changes in tissue ADC between 36 degrees C and 43 degrees C (temperatures below the threshold of irreversible tissue damage) regardless of ADC anisotropy or physiological response. Above temperatures of 43 degrees for extended periods of time (30-60 minutes) there may well be changes in this relationship which we will be able to observe and relate to irreversible tissue thermal damage. After establishment of the relationship between temperature and ADC over the hyperthermia range in animals we propose to begin Phase 3: MRI monitored hyperthermia in human patients to demonstrate the feasible of this method in human subjects and to confirm the relationship between ADC and temperature in human tissues.